Efficacy and Safety of Sorafenib Therapy on Metastatic Renal Cell Carcinoma in Korean Patients: Results from a Retrospective Multicenter Study

PLOS ONE, Dec 2019

Objective To evaluate the efficacy and safety of sorafenib for Korean patients with metastatic renal cell carcinoma (mRCC). Methods A total of 177 mRCC patients using sorafenib as first- (N = 116), second- (N = 43), and third-line (N = 18) therapies were enrolled from 11 Korean centers between 2006 and 2012. The patient characteristics, therapy duration, tumor response, disease control rate, and tolerability were assessed at baseline and at routine follow-ups, and the progression-free survival (PFS) and overall survival (OS) times and rates were analyzed. Results Among all patients, 18 (10.2%) stopped sorafenib treatment for a median of 1.7 weeks, including 15 (8.5%) who discontinued the drug, while 40 (22.6%) and 12 (6.8%) patients required dose reductions and drug interruptions, respectively. Severe adverse events (AEs) or poor compliance was observed in 64 (36.2%) patients, with 118 (7.4%) ≥grade 3 AEs. During the treatment, one myocardial infarction was observed. The number of ≥grade 3 AEs in the first-line sorafenib group was 71 (6.8% of the total 1048 AEs). During a median follow-up of 17.2 months, the radiologically confirmed best objective response rate, disease control rate, median PFS, and median OS were 22.0%, 53.0%, 6.4 months (95% confidence interval [CI], 5.2–8.9), and 32.6 months (95% CI, 27.3–63.8) for the total 177 sorafenib-treated patients, respectively, and 23.2%, 56.0%, 7.4 months (95% CI, 5.5–10.5), and not reached yet (95% CI, 1.0–31.1) for the first-line sorafenib group, respectively. Conclusions Sorafenib produced tolerable safety, with a ≥grade 3 AE rate of 7.4% and an acceptable disease control rate (53.0%) in Korean mRCC patients.

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Efficacy and Safety of Sorafenib Therapy on Metastatic Renal Cell Carcinoma in Korean Patients: Results from a Retrospective Multicenter Study

August Efficacy and Safety of Sorafenib Therapy on Metastatic Renal Cell Carcinoma in Korean Patients: Results from a Retrospective Multicenter Study Sung Han Kim 0 1 Sohee Kim 0 1 Byung-Ho Nam 0 1 Sang Eun Lee 0 1 Choung Soo Kim 0 1 Ill Young Seo 0 1 Tae Nam Kim 0 1 Sung-Hoo Hong 0 1 Tae Gyun Kwon 0 1 Seong Il Seo 0 1 Kwan Joong Joo 0 1 Kanghyon Song 0 1 Cheol Kwak 0 1 Jinsoo Chung 0 1 0 1 Departments of Urology, Center for Prostate Cancer, National Cancer Center , Goyang, Korea, 2 Biometric Research Branch , Center for Prostate Cancer, National Cancer Center , Goyang , Korea , 3 Seoul National University Bundang Hospital, SeongNam, Korea, 4 Asan Medical Center , Seoul , Korea , 5 Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul , Korea , 6 Pusan National University Hospital , Busan, Korea, 7 Seoul St. Mary's Hospital , Seoul , Korea , 8 School of Medicine, Kyungpook National University , Daegu , Korea , 9 Wonkwang University School of Medicine and Hospital , Iksan , Korea , 10 Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine , Seoul , Korea , 11 Korea Cancer Center Hospital , Seoul , Korea , 12 Seoul National University Hospital , Seoul , Korea 1 Editor: Jung Weon Lee, Seoul National University , REPUBLIC OF KOREA - Funding: This investigator-initiated research was supported with funding by a grant from Bayer Healthcare Pharmaceuticals, Korea (Grant No. Asan cell carcinoma (mRCC). To evaluate the efficacy and safety of sorafenib for Korean patients with metastatic renal patient characteristics, therapy duration, tumor response, disease control rate, and tolerability were assessed at baseline and at routine follow-ups, and the progression-free survival (PFS) and overall survival (OS) times and rates were analyzed. Among all patients, 18 (10.2%) stopped sorafenib treatment for a median of 1.7 weeks, including 15 (8.5%) who discontinued the drug, while 40 (22.6%) and 12 (6.8%) patients required dose reductions and drug interruptions, respectively. Severe adverse events (AEs) or poor compliance was observed in 64 (36.2%) patients, with 118 (7.4%) During the treatment, one myocardial infarction was observed. The number of AEs in the first-line sorafenib group was 71 (6.8% of the total 1048 AEs). During a median follow-up of 17.2 months, the radiologically confirmed best objective response rate, disease control rate, median PFS, and median OS were 22.0%, 53.0%, 6.4 months (95% confidence 2012-09). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Co-author Ill Young Seo is employed by Samsung Medical Center. Coauthor Kwan Joong Joo is employed by Kangbuk Samsung Hospital. Samsung Medical Center and Kangbuk Samsung Hospital provided support in the form of salaries for authors IYS and KJJ, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. Competing Interests: This investigator-initiated research was supported with funding by a grant from Bayer Healthcare Pharmaceuticals. Co-author Ill Young Seo is employed by Samsung Medical Center. Co-author Kwan Joong Joo is employed by Kangbuk Samsung Hospital. The corresponding author (Dr. Jinsoo Chung) and one of the co-author named Dr Choung-Soo Kim have acted as consultants for Pfizer, Bristol-Myers Squibb, and Taiho, and have received advisory and/or speaker fees from Bayer, Bristol-Myers Squibb, and Taiho. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. The other authors declare that they do not have anything to disclose regarding funding or conflicts of interests with respect to this manuscript. interval [CI], 5.2–8.9), and 32.6 months (95% CI, 27.3–63.8) for the total 177 sorafenibtreated patients, respectively, and 23.2%, 56.0%, 7.4 months (95% CI, 5.5–10.5), and not reached yet (95% CI, 1.0–31.1) for the first-line sorafenib group, respectively. Conclusions Sorafenib produced tolerable safety, with a grade 3 AE rate of 7.4% and an acceptable disease control rate (53.0%) in Korean mRCC patients. Until the early 2000s, which saw the advent of targeted therapy (TT), metastatic renal cell carcinoma (mRCC) was considered a dismal disease, owing to its high resistance to chemotherapy and poor responses (<20%) to cytokine therapy, the first-line systemic therapy for mRCC patients at that time [1]. Moreover, many patients were unable to receive cytokine therapy, particularly interleukin-2, due to toxicity, resulting in 5-year overall survival (OS) rates of only 10–22% [2]. After the introduction of several new agents, the standard first-line treatment for advanced RCC has shifted to TT. Among the TTs, sorafenib (Nexavar, Bayer Heal (...truncated)


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Sung Han Kim, Sohee Kim, Byung-Ho Nam, Sang Eun Lee, Choung Soo Kim, Ill Young Seo, Tae Nam Kim, Sung-Hoo Hong, Tae Gyun Kwon, Seong Il Seo, Kwan Joong Joo, Kanghyon Song, Cheol Kwak, Jinsoo Chung. Efficacy and Safety of Sorafenib Therapy on Metastatic Renal Cell Carcinoma in Korean Patients: Results from a Retrospective Multicenter Study, PLOS ONE, 2015, Volume 10, Issue 8, DOI: 10.1371/journal.pone.0135165